Project Summary/Abstract The La Jolla Institute for Allergy and Immunology has dedicated itself to understanding the fundamental mechanisms of the immune system and how this powerful ecosystem can both protect and destroy the human body. It is for this reason that in 1989 the Institute was formed, and with all of the implications the immune system has in tomorrow's breakthroughs, is now more important than ever. The effort to cure disease, create effective vaccines, and use our own bodies to do it, will require the brightest minds and the most advanced technologies. It is for this reason that the researchers of LJI are requesting the support needed to secure the latest next-generation sequencing system released by Illumina: NovaSeq 5000. Over the last decade, NGS technology has altered the landscape of research and allowed us to ask and answer questions that had not previously been possible. This ability has led to the exponential growth in the use of our NGS core facility, with current instrumentation running well above capacity, and the future pipeline of NIH-funded projects expected to push capacity to unsustainable levels. In addition to the advances in technology that the NovaSeq 5000 brings to our projects, this new system will also save taxpayers in supply costs, with an estimated payback within three years. This kind of investment is important in the trust that we receive from the public; one that is both cost effective and delivers on the expectations of results. The NovaSeq 5000 is also fundamentally simpler to use than previous sequencing systems, allowing more researchers to become familiar and comfortable with this very important technology. For these many reason, we feel the urgency and importance of putting in this application for support of a NovaSeq 5000.